GLP-1 Agonists Are Associated With a Significant Reduction in Breast Cancer Incidence in Women
Purpose
Excess weight is a key modifiable risk factor for breast cancer. Glucagon-like peptide-1 receptor agonists (GLP-1) promote weight loss and improve metabolic health, but their effect on breast cancer risk remains unclear.
Methods
We conducted a retrospective cohort study from January 1, 2022, to June 30, 2025, using electronic health records. We identified 217,624 unique women who underwent breast imaging; restricting to ages 45–80 years with a BMI ≥25 and a documented imaging outcome (n = 111,646; median age 61 years). The primary outcome was breast cancer detection. GLP-1 use was defined as a first prescription before the examination date. To address potential confounding, we performed one-to-one, case-control matching using propensity scores based on age, race, ethnicity, highest BMI, breast density, and history of type 2 diabetes.
Results
GLP-1 exposure was associated with a lower incidence of breast cancer (OR 0.649 [95% CI, 0.569–0.741]; P < .0001). In the matched logistic regression (30,528 observations; 600 cancer cases), GLP-1 exposure was associated with a lower breast cancer incidence (OR 0.695 [95% CI, 0.590–0.819]; P < .0001).
Conclusion
In this large observational study of women undergoing breast imaging at a major academic center and affiliated sites, GLP-1 treatment was associated with a lower incidence of breast cancer, independent of age, race, ethnicity, BMI, breast density, and diabetes. The findings support the need for prospective trials investigating GLP-1 agonists for breast cancer prevention.
Introduction
There is extensive evidence that weight influences breast cancer risk and that lifestyle modification, including weight loss, can reduce this risk. GLP-1 agonists promote weight loss and improve markers of metabolic health. However, the impact of GLP-1 agonists on breast cancer risk among women eligible for screening remains uncertain. Interest in whether GLP-1 agonists could reduce cancer risk has grown significantly, with Cancer Research UK hosting a debate at its Cancer Prevention Conference in June 2025 on the topic. The discussion underscored research indicating benefits for obesity-related cancers, but emphasized that current evidence remains insufficient for public health recommendations.
Bariatric surgery leads to sustained weight loss and reduction in the risk of breast cancer. A meta-analysis comparing 511,585 patients who underwent bariatric surgery with 1,889,746 controls found that bariatric surgery was associated with a reduced incidence of breast cancer (RR 0.56 [95% CI, 0.44–0.71]; P < .00001) over at least 3 years of follow-up. Although effective, bariatric surgery is not practical for cancer prevention at a population level.
GLP-1 agonists function by activating receptors for the incretins GLP-1 and/or GIP. These endogenous gut peptides enhance insulin secretion after meals, decrease food intake, and lower blood glucose levels. Mounting evidence suggests GLP-1 agonists may also offer benefits beyond weight loss, including reductions in systemic inflammation. Given that inflammation is a hallmark of cancer, there is considerable interest in exploring these compounds for their potential cancer-preventative effects.
In breast cancer, studies have shown direct and/or indirect inhibition of tumor growth both in vitro and in vivo. For example, the GLP-1 agonists exendin-4 and liraglutide activate AMPK in breast cancer cells, leading to impaired glycolytic metabolism and decreased cell proliferation. Liraglutide also inhibited proliferation in estrogen receptor–positive and triple-negative breast cancer cells through inhibition of DNA methyltransferase enzymes. Tirzepatide suppressed triple-negative breast cancer in a model of obese, tumor-bearing mice, with inhibition in tumor growth largely attributable to weight loss.
Methods
After receiving approval from the University of Pennsylvania institutional review board (#852383), we conducted a retrospective cohort study from January 1, 2022, to June 30, 2025, using electronic health records from a large, diverse health system including academic and community sites in Delaware Valley, Central Jersey, and South Central Pennsylvania. The primary outcome was a malignant breast pathology diagnosis during the study period.
GLP-1 agonist use was defined as a first prescription before the examination date. BMI was recorded as the maximum for each patient from January 1, 2017, to June 30, 2025. To minimize potential confounding, we performed one-to-one case-control matching with log propensity scores using the greedy nearest-neighbor approach in SAS 9.4, matching on race, ethnicity, breast density, history of type 2 diabetes, age, and BMI.
Results
We identified 217,624 unique women who underwent breast imaging from January 1, 2022, to June 30, 2025. Restricting to women aged 45–80 years with BMI ≥25 and a documented imaging outcome yielded 111,646 women with a median age of 61 years. The matched data set includes 30,528 observations.
A total of 2,628 (2.35%) women were diagnosed with breast cancer during the study period. Of the total, 15,264 (13.67%) had GLP-1 agonist exposure and 96,382 (86.33%) did not. Among those exposed to GLP-1 agonists, 247 (1.62%) developed breast cancer. Among women without GLP-1 exposure, 2,381 (2.47%) developed breast cancer.
GLP-1 agonist exposure was associated with a lower incidence of breast cancer (OR 0.649 [95% CI, 0.569–0.741]; P < .0001). In the matched logistic regression analysis (30,528 observations; 600 cancer cases), GLP-1 agonist exposure was associated with a lower incidence of breast cancer (OR 0.695 [95% CI, 0.590–0.819]; P < .0001).
The absolute risk reduction (ARR) in the matched data set was 0.69% (95% CI, 0.38–1.01). In subgroup analyses, the OR for cancer with GLP-1 exposure compared with no exposure was 0.767 (95% CI, 0.597–0.986; P = .0384) for Black or African American women and 0.674 (95% CI, 0.536–0.847; P = .0007) for white women.
Discussion
To our knowledge, this is the first observational analysis in a population exclusively including women eligible for breast cancer screening to assess whether GLP-1 agonists are associated with a reduced incidence of breast cancer. We observed an approximately 30% decrease in breast cancer incidence, a reduction comparable with early studies of tamoxifen (38% reduction; P < .0001), noting that tamoxifen also increased endometrial cancer by 2.4-fold and venous thromboembolic events by 1.9-fold.
Additional options are needed for breast cancer preventative care, as the USPSTF concluded that the side effects of raloxifene and tamoxifen outweigh the benefits in women who are not at high risk of breast cancer. GLP-1 agonists have the potential to offer some degree of protection without these risks, although they have their own adverse event profile, largely mild-to-moderate and transient nausea, vomiting, diarrhea, and constipation, as well as a 1.5-fold increase in gallbladder and biliary events.
Levy et al reported a similar reduction in breast cancer incidence with GLP-1 agonists (1.1 million patients, hazard ratio 0.72 [95% CI, 0.64–0.82]), although that study had limitations including a relatively nondiverse cohort (three-quarters white). In contrast, some meta-analyses combining clinical trials have not found a significant association, but these were limited by very low cancer case counts per cohort.
Several mechanistic observations suggest that GLP-1/GIP receptor signaling may be relevant to breast cancer biology. Higher tumor GLP1R expression was associated with improved overall survival in breast and other cancers. Impaired GIP receptor signaling has been associated with increased breast cancer risk. There is also limited evidence that GLP-1 agonists can improve survival among women with breast cancer and type 2 diabetes.
Although these findings are exciting, observational studies have inherent limitations. We attempted to address biases with cohort-matched analyses, but we did not specifically examine the impact of exposure duration or drug dosage on cancer development. Additionally, patients received different drug formulations and doses. There is also a potential ascertainment bias, as some women in the control group may have obtained GLP-1 agonists outside of our health system, including from compounding pharmacies.
Overweight perimenopausal and postmenopausal women represent an important target population for weight-based modification to reduce cancer risk. Only a prospective randomized trial can adequately answer these questions and provide practice-changing evidence. We propose advancing to a randomized trial to evaluate a trifecta of prevention: cancer, heart disease, and the metabolic changes and symptomatology associated with menopause. There is perhaps no singular preventative intervention with such broad potential to improve women's health.
Acknowledgment
We thank the University of Pennsylvania Cancer Informatics Shared Resource for database curation (RRID: SCR_022715) and Mahsa Kiani for assistance with graphic design.
